Calcitonin gene-related peptide is a depressor in subtotal nephrectomy hypertension.
We previously demonstrated that the neuronal expression of calcitonin gene-related peptide (CGRP), a potent vasodilator, is increased in deoxycorticosterone-salt-induced hypertension where it acts as a compensatory vasodilator to attenuate the elevated blood pressure. To determine whether CGRP is playing a similar role in subtotal nephrectomy-salt-induced hypertension, hypertension was induced in Sprague-Dawley rats (n=6) by subtotal nephrectomy and 1.0% saline drinking water. Control rats (n=6) were sham operated and given tap water to drink. CGRP(8-37), a CGRP receptor antagonist, was used to assess the hemodynamic role of CGRP in this setting. CGRP mRNA and peptide levels in dorsal root ganglia were also determined. Three weeks after either protocol, all rats had intravenous (for drug administration) and arterial (for continuous mean arterial pressure monitoring) catheters surgically placed and were studied in the conscious, unrestrained state. CGRP(8-37) (3.2 or 6.4 x 10(4) pmol/L in 0.1 mL saline) and vehicle were administered intravenously to all rats. Baseline mean arterial pressure was higher in the subtotal nephrectomized rats compared with the controls (173+/-5 versus 113+/-5 mm Hg, P<.001). Vehicle administration did not change mean arterial pressure in either group, and CGRP(8-37) administration did not alter mean arterial pressure in the normotensive group. In contrast, CGRP(8-37) administration to the subtotal nephrectomized rats rapidly increased the already elevated mean arterial pressure at both the 3.2 x 10(4) pmol/L dose (7.8+/-1.1 mm Hg, P<.05) and the 6.4 x 10(4) pmol/L dose (9.6+/-0.8 mm Hg, P<.01). CGRP mRNA and peptide levels in the dorsal root ganglia were not significantly different between the two groups. These data suggest that in subtotal nephrectomy-salt-induced hypertension, CGRP may play a compensatory depressor role in an attempt to lower the elevated blood pressure.
Supowit
S C
SC
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555-1065, USA.
Zhao
H
H
Hallman
D M
DM
DiPette
D J
DJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000494:pharmacology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D005727:Ganglia, Spinal / Q000378:metabolism*; D006801:Humans; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D008297:Male; D009392:Nephrectomy; D009474:Neurons / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary; D014158:Transcription, Genetic
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010446:Peptide Fragments; D012333:RNA, Messenger; D012982:Sodium, Dietary; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide